title: Growth hormone treatment for Turner syndrome in Australia reveals that younger age and increased dose interact to improve response.
abstract: OBJECTIVE
  To investigate response to growth hormone (GH) in the first, second and third years of treatment in the total clinical cohort of Turner syndrome (TS) patients in Australia.
  
  
  BACKGROUND
  Short stature is the most common clinical manifestation of TS. GH treatment improves growth.
  
  
  METHODS
  Response was measured for each year of treatment. Stepwise multiple regression analyses were used to identify factors that significantly influenced response.
  
  
  METHODS
  Prepubertal TS patients who completed 1 year (n=176), 2 years (n=148), or 3 years (n=117) of treatment and were currently receiving GH.
  
  
  METHODS
  Change in TS specific Height Standard Deviation Score (ΔTSZ) was the main response variable used. Major influencing variables considered included dose, starting age and height, BMI, bone age delay, karyotype, parental height, and interactions between dose and starting age or height.
  
  
  RESULTS
  Response was greatest in first year and declined thereafter (median ΔTSZ: 1st year= +0·705, 2nd year= +0·439, 3rd year= +0·377) despite the median dose increasing [1st year= 5·5 mg/m(2) /week (0·23 mg/kg/week), 2nd year= 6·4(0·24), 3rd year= 7·2(0·26)]. An Age*Dose interaction was identified influencing first, second year, and total ΔTSZ. The ΔTSZ over 3 years was significantly influenced by first-year dose. Dose increments only attenuated the general decline in response. An acceptable first-year response (ΔTSZ>1·01) was achieved by only 17·6% of patients.
  
  
  CONCLUSIONS
  Growth response is greatest and most influenced by dose in the first year. Dose in first year is a major factor contributing to total response. A starting Age*Dose interaction effect was observed such that young girls on a high dose respond disproportionately better. Optimal GH treatment of short stature in TS thus requires early initiation with the highest safe dose in the first year.
authors.affiliation: The Children's Nutrition Research Centre, Discipline of Paediatrics and Child Health, School of Medicine, The University of Queensland, Herston, Qld., Australia. i.hughes@uq.edu.au
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hughes
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Choong
authors.forename: Mark
authors.initials: M
authors.lastname: Harris
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Ambler
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Cutfield
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hofman
authors.forename: Chris T
authors.initials: CT
authors.lastname: Cowell
authors.forename: George
authors.initials: G
authors.lastname: Werther
authors.forename: Andrew
authors.initials: A
authors.lastname: Cotterill
authors.forename: Peter S W
authors.initials: PS
authors.lastname: Davies
mesh_terms: D000367:Age Factors; D001315:Australia; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D011627:Puberty; D014424:Turner Syndrome / Q000188:drug therapy*
chemical_list: D019382:Human Growth Hormone